RESUMEN
Remdesivir (RDV) is the only antiviral drug so far approved for COVID-19 therapy by the FDA. However its efficacy is limited in vivo due to its low stability in presence of plasma. This paper compared the stability of RDV encapsulated with our platform technology based polymer NV-387 (NV-CoV-2), in presence of plasma in vitro and in vivo. Furthermore, a non- clinical pharmacology studies of NV-CoV-2 (Polymer) and NV-CoV-2-R (Polymer encapsulated Remdesivir) in both NL-63 infected and uninfected rats were done. In an in vitro cell culture model experiment, antiviral activity of NV-CoV-2 and NV-CoV-2-R are also compared with RDV. The results are (i) NV-CoV-2 polymer encapsulation protects RDV from plasma- mediated catabolism in vitro and in vivo, too. (ii) Body weight measurements of the normal (uninfected) rats after administration of the test materials (NV-CoV-2, and NV-CoV-2-R) show no toxic effects on them. (iii) NL-63 infected rats body weights and their survival length were like uninfected rats after treatment with NV-CoV-2 and NV-CoV-2-R, and the efficacy as an antiviral regimen were found in the order as below: NV-CoV-2-R > NV-CoV-2 > RDV. In brief, our platform technology based NV-387-encapsulated-RDV (NV-CoV-2-R) drug has a dual effect on coronaviruses. First, NV-CoV-2 itself as an antiviral regimen. Secondly, RDV is protected from plasma-mediated degradation in transit, rendering altogether the safest and an efficient regimen against COVID-19.
RESUMEN
So far, there are seven coronaviruses identified that infect humans and only 4 of them belong to the beta family of coronavirus (HCoV-HKU1, SARS-CoV-2, MERS-CoV and SARS-CoV). SARS family are known to cause severe respiratory disease in humans. In fact, SARS-CoV-2 infection caused a pandemic COVID-19 disease with high morbidity and mortality. Remdesivir (RDV) is the only antiviral drug so far approved for COVID-19 therapy by the FDA. However, the efficacy of RDV in vivo is limited due to its low stability in presence of plasma. This is the report of analysis of the non-clinical pharmacology study of NV-CoV-2 (Polymer) and NV-CoV-2-R (Polymer encapsulated Remdesivir) in both infected and uninfected rats with SARS-CoV-2. Detection and quantification of NV-CoV-2-R in plasma samples was done by MS-HPLC chromatography analyses of precipitated plasma samples from rat subjects. O_LINV-CoV-2-R show RDV peak in MS-HPLC chromatography, whereas only NV-CoV-2 does not show any RDV-Peak, as expected. C_LIO_LINV-CoV-2 polymer encapsulation protects RDV in vivo from plasma-mediated catabolism. C_LIO_LIBody weight measurements of the normal (uninfected) rats after administration of the test materials (NV-CoV-2, and NV-CoV-2-R) show no toxic effects on them. C_LI Our platform technology based NV-387-encapsulated-RDV (NV-CoV-2-R) drug has a dual effect on coronaviruses. First, NV-CoV-2 itself as an antiviral regimen. Secondly, RDV is protected from plasma-mediated degradation in transit, rendering altogether the safest and an efficient regimen against COVID-19.
RESUMEN
As of today seven coronaviruses were identified to infect humans, out of which only 4 of them belongs to beta family of coronavirus, like HCoV-HKU1, SARS-CoV-2, MERS-CoV and SARS-CoV. SARS family of viruses were known to cause severe respiratory disease in humans. SARS-CoV-2 infection causes pandemic COVID-19 disease with high morbidity and mortality. Remdesivir (RDV) is the only antiviral drug so far approved for Covid-19 therapy by FDA. However its efficacy is limited in vivo due to its low stability in presence of Plasma. Here we show the stability of RDV encapsulated with our platform technology based polymer NV-387 (NV-CoV-2-R), in presence of Plasma in vitro in comparison to naked RDV when incubated in plasma. The potential use of this polymer in vivo will be discussed, here.
RESUMEN
PURPOSE: Recently, a new specific organ dose adaption and reduction protocol, or SODAR tool (X-CARE, Siemens Healthcare), which reduces dose to the anterior aspect of the body of patients, was installed on our computed tomographic scanner. The purpose of this pilot project was to evaluate image quality and dose distribution in the acquired data with the new protocol. MATERIALS AND METHODS: Sixteen consecutive patients were scanned with the new SODAR head protocol. The findings were compared with 16 matched patients who were imaged with the standard computed tomographic head trauma protocol. Image quality was assessed qualitatively using a scale of 1 to 4 (1, excellent; 2, good; 3, fair; 4, nondiagnostic). Additionally, 1-cm regions of interest were placed in the white matter of the cerebral hemispheres, the cerebellar hemispheres, and the brain stem at the level of the pons for a quantitative analysis. The standard deviation of each measurement was recorded as an indicator for image noise. Dose measurement trials were performed using optically stimulated luminescence dosimeters on head phantoms and then on patients. RESULTS: Subjective image quality ranged between 1 and 3; no scan areas were considered nondiagnostic. Overall image quality of the posterior fossa averaged at 1.656 was slightly reduced compared to the cerebral hemispheres (mean, 1.141). The mean standard protocol brain stem image quality was 1.604, with only minimal deterioration to 1.708 in the SODAR group.No significant difference in image noise could be found between the SODAR group with a mean noise of 4.515 and standard images with a mean of 4.721 (P > 0.05).The dose to the anterior aspect of the patient was lowered to 3.2 mGy compared to 4.5 mGy on the lateral aspect of the scan (P > 0.05). To compensate for the photon loss in the posterior aspect, the dose has to be slightly increased to a mean of 6 mGy, but overall, a significant dose reduction with stable image quality could be achieved by reducing the dose length product from 1489 to 1347 mGy·cm using SODAR (P < 0.0001). CONCLUSION: Using the SODAR protocol resulted not only in an impressive 46% to 59% frontal dose reduction but also in the overall dose reduction. This dose reduction was obtained without sacrificing image quality, providing diagnostic images of the brain while protecting radiosensitive structures like the eye lenses in trauma brain imaging. Future applications will be reducing dose to other radiosensitive structures such as the thyroid gland and breast tissue from potentially harmful low-energy radiation without compromising image quality.